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1.
Neuro Oncol ; 2019 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-31883020

RESUMO

BACKGROUND: Controversy exists as to what may be defined as standard of care (including markers for stratification) for patients with Atypical Teratoid Rhabdoid Tumors (ATRT). The European Rhabdoid Registry, EU-RHAB, recruits uniformly treated patients and offers standardized genetic and DNA methylation analyses. METHODS: Clinical, genetic and treatment data of 143 patients from 13 European countries were analyzed (2009 - 2017). Therapy consisted of surgery, anthracycline-based induction and either radiotherapy or high dose chemotherapy following a consensus among European experts. FISH, MLPA and sequencing were employed for assessment of somatic and germline mutations in SMARCB1. Molecular subgroups (ATRT-SHH, -TYR and -MYC) were determined using DNA-methylation arrays resulting in profiles of 84 tumors. RESULTS: Median age at diagnosis of 67 girls and 76 boys was 29.5 months. 5-year overall survival (OS) and event-free survival (EFS) were 34.7±4.5% and 30.5±4.2%. Tumors displayed allelic partial/whole gene deletions (66%; 122/186 alleles) or single nucleotide variants (34%; 64/186 alleles) of SMARCB1. Germline mutations were detected in 26% of ATRT (30/117). The patient cohort consisted of 47% ATRT-SHH (39/84), 33% ATRT-TYR (28/84), and 20% ATRT-MYC 17/84). Age <1 year, non-TYR signature (ATRT-SHH or -MYC), metastatic or synchronous tumors, germline mutation, incomplete remission and omission of radiotherapy were negative prognostic factors in univariate analyses (p<0.05). An adjusted multivariate model identified age <1 year and a non-TYR signature as independent negative predictors of OS: high risk (<1 year + non-TYR; 5-year OS = 0%), intermediate risk (<1 year + ATRT-TYR or ≥1 year + non-TYR; 5-year OS = 32.5±8.7%) and standard risk (≥1 year + ATRT-TYR, 5-year OS = 71.5±12.2%). CONCLUSIONS: Age and molecular subgroup status are independent risk factors for survival in children with ATRT. Our model warrants validation within future clinical trials.

2.
Soft Matter ; 15(42): 8512-8524, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31633148

RESUMO

The self-assembly of small colloidal clusters, so-called colloidal molecules, into crystalline materials has proven extremely challenging, the outcome often being glassy, amorphous states where positions and orientations are locked. In this paper, a new type of colloidal molecule is therefore prepared, assembled from poly(N-isopropylacrylamide) (PNIPAM)-based microgels that due to their well documented softness and temperature-response allow for greater defect tolerance compared to hard spheres and for convenient in situ tuning of size, volume fraction and inter-particle interactions with temperature. The microgels (B) are assembled by electrostatic adsorption onto oppositely charged, smaller-sized microgels (A), where the relative size of the two determines the valency (n) of the resulting core-satellite ABn-type colloidal molecules. Following assembly, a microfluidic deterministic lateral displacement (DLD) device is used to effectively isolate AB4-type colloidal molecules of tetrahedral geometry that possess a repulsive-to-attractive transition on crossing the microgels' volume phase transition temperature (VPTT). These soft, temperature-responsive colloidal molecules constitute highly promising building blocks for the preparation of new materials with emergent properties, and their optical wavelength-size makes them especially interesting for optical applications.

3.
J Phys Chem B ; 123(43): 9260-9271, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31584820

RESUMO

Small clusters of spherical colloids that mimic real molecules, so-called colloidal molecules, hold great promise as building blocks in bottom-up routes to new materials. However, their typical hard sphere nature has hampered their assembly into ordered structures, largely due to a lack of control in the interparticle interactions. To provide easy external control of the interactions, the present work focuses on the preparation of colloidal molecules from temperature-responsive microgel particles that undergo a transition from a soft repulsive to a short-range attractive state as their characteristic volume phase transition temperature (VPTT) is crossed. Preparation of the colloidal molecules starts with the use of a droplet-based microfluidics device to form highly uniform water-in-oil (W/O) emulsion droplets containing, on average and with a narrow distribution, four microgels per droplet. Evaporation of the water then leads to the formation of colloidal molecule-like clusters, which can be harvested following cross-linking and phase transfer. We use a mixture of two types of microgels, one based on poly(N-isopropylacrylamide) (PNIPAM) and the other on poly(N-isopropylmethacrylamide) (PNIPMAM), to prepare bicomponent colloidal molecules, and show that the difference in VPTT between the two allows for induction of attractive interparticle interactions between the PNIPAM interaction sites at temperatures in between the two VPTTs, analogous to the interactions among patchy biomacromolecules such as many proteins.

4.
J Neurooncol ; 145(1): 177-184, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31522324

RESUMO

INTRODUCTION: Diffuse intrinsic pontine glioma (DIPG) is a rare clinically, neuro-radiologically, and molecularly defined malignancy of the brainstem with a median overall survival of approximately 11 months. Our aim is to evaluate the current tendency for its treatment in Europe in order to develop (inter)national consensus guidelines. METHODS: Healthcare professionals specialized in DIPG were asked to fill in an online survey with questions regarding usual treatment strategies at diagnosis and at disease progression in their countries and/or their centers, respectively. RESULTS: Seventy-four healthcare professionals responded to the survey, of which 87.8% were pediatric oncologists. Only 13.5% of the respondents biopsy all of their patients, 41.9% biopsy their patients infrequently. More than half of the respondents (54.1%) treated their patients with radiotherapy only at diagnosis, whereas 44.6% preferred radiotherapy combined with chemotherapy. When the disease progresses, treatment strategies became even more diverse, and the tendency for no treatment increased from 1.4% at diagnosis to 77.0% after second progression. 36.5% of the healthcare professionals treat children younger than 3 years differently than older children at diagnosis. This percentage decreased, when the disease progresses. Most of the participants (51.4%) included less than 25% of their patients in clinical trials. CONCLUSION: This survey demonstrates a large heterogeneity of treatment regimens, especially at disease progression. We emphasize the need for international consensus guidelines for the treatment of DIPG, possible by more collaborative clinical trials.

5.
Lab Chip ; 19(3): 513-523, 2019 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-30632599

RESUMO

Skeletal stem cells (SSCs) are present in bone marrow (BM) and offer great potential for bone regenerative therapies. However, in the absence of a unique marker, current sorting approaches remain challenging in the quest for simple strategies to deliver SSCs with consistent regeneration and differentiation capacities. Microfluidics offers the possibility to sort cells marker-free, based on intrinsic biophysical properties. Recent studies indicate that SSCs are stiffer than leukocytes and are contained within the larger cell fraction in BM. This paper describes the use of deterministic lateral displacement (DLD) to sort SSCs based on cell size and stiffness. DLD is a technology that uses arrays of micropillars to sort cells based on their diameter. Cell deformation within the device can change the cell size and affect sorting - here evidenced using human cell lines and by fractionation of expanded SSCs. Following sorting, SSCs remained viable and retained their capacity to form clonogenic cultures (CFU-F), indicative of stem cell potential. Additionally, larger BM cells showed enhanced capacity to form CFU-F. These findings support the theory that SSCs are more abundant within the larger BM cell fraction and that DLD, or other size-based approaches, could be used to provide enriched SSC populations with significant implications for stem cell research and translation to the clinic.


Assuntos
Células da Medula Óssea/citologia , Separação Celular/instrumentação , Dispositivos Lab-On-A-Chip , Células-Tronco/citologia , Fenômenos Biomecânicos , Técnicas de Cultura de Células , Desenho de Equipamento , Humanos
7.
PLoS One ; 13(1): e0190605, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29351300

RESUMO

We present an agent-based model of wood markets and show our efforts to validate this model using empirical data from different sources, including interviews, workshops, experiments, and official statistics. Own surveys closed gaps where data was not available. Our approach to model validation used a variety of techniques, including the replication of historical production amounts, prices, and survey results, as well as a historical case study of a large sawmill entering the market and becoming insolvent only a few years later. Validating the model using this case provided additional insights, showing how the model can be used to simulate scenarios of resource availability and resource allocation. We conclude that the outcome of the rigorous validation qualifies the model to simulate scenarios concerning resource availability and allocation in our study region.


Assuntos
Comércio , Análise de Sistemas , Madeira , Modelos Teóricos , Suíça
8.
Pathogens ; 6(4)2017 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-28981471

RESUMO

African trypanosomes are responsible for significant levels of disease in both humans and animals. The protozoan parasites are free-living flagellates, usually transmitted by arthropod vectors, including the tsetse fly. In the mammalian host they live in the bloodstream and, in the case of human-infectious species, later invade the central nervous system. Diagnosis of the disease requires the positive identification of parasites in the bloodstream. This can be particularly challenging where parasite numbers are low, as is often the case in peripheral blood. Enriching parasites from body fluids is an important part of the diagnostic pathway. As more is learned about the physicochemical properties of trypanosomes, this information can be exploited through use of different microfluidic-based approaches to isolate the parasites from blood or other fluids. Here, we discuss recent advances in the use of microfluidics to separate trypanosomes from blood and to isolate single trypanosomes for analyses including drug screening.

9.
BMC Cancer ; 17(1): 439, 2017 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-28637445

RESUMO

BACKGROUND: Central nervous system tumours constitute 25% of all childhood cancers; more than half are located in the posterior fossa and surgery is usually part of therapy. One of the most disabling late effects of posterior fossa tumour surgery is the cerebellar mutism syndrome (CMS) which has been reported in up to 39% of the patients but the exact incidence is uncertain since milder cases may be unrecognized. Recovery is usually incomplete. Reported risk factors are tumour type, midline location and brainstem involvement, but the exact aetiology, surgical and other risk factors, the clinical course and strategies for prevention and treatment are yet to be determined. METHODS: This observational, prospective, multicentre study will include 500 children with posterior fossa tumours. It opened late 2014 with participation from 20 Nordic and Baltic centres. From 2016, five British centres and four Dutch centres will join with a total annual accrual of 130 patients. Three other major European centres are invited to join from 2016/17. Follow-up will run for 12 months after inclusion of the last patient. All patients are treated according to local practice. Clinical data are collected through standardized online registration at pre-determined time points pre- and postoperatively. Neurological status and speech functions are examined pre-operatively and postoperatively at 1-4 weeks, 2 and 12 months. Pre- and postoperative speech samples are recorded and analysed. Imaging will be reviewed centrally. Pathology is classified according to the 2007 WHO system. Germline DNA will be collected from all patients for associations between CMS characteristics and host genome variants including pathway profiles. DISCUSSION: Through prospective and detailed collection of information on 1) differences in incidence and clinical course of CMS for different patient and tumour characteristics, 2) standardized surgical data and their association with CMS, 3) diversities and results of other therapeutic interventions, and 4) the role of host genome variants, we aim to achieve a better understanding of risk factors for and the clinical course of CMS - with the ultimate goal of defining strategies for prevention and treatment of this severely disabling condition. TRIAL REGISTRATION: Clinicaltrials.gov : NCT02300766 , date of registration: November 21, 2014.


Assuntos
Neoplasias Cerebelares/cirurgia , Neoplasias Infratentoriais/cirurgia , Mutismo/fisiopatologia , Complicações Pós-Operatórias/fisiopatologia , Adolescente , Neoplasias Cerebelares/complicações , Neoplasias Cerebelares/epidemiologia , Neoplasias Cerebelares/fisiopatologia , Cerebelo/fisiopatologia , Cerebelo/cirurgia , Criança , Pré-Escolar , Dinamarca/epidemiologia , Feminino , Humanos , Lactente , Neoplasias Infratentoriais/complicações , Neoplasias Infratentoriais/epidemiologia , Neoplasias Infratentoriais/fisiopatologia , Masculino , Mutismo/epidemiologia , Mutismo/etiologia , Procedimentos Neurocirúrgicos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Fatores de Risco
10.
Neuro Oncol ; 19(10): 1398-1407, 2017 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-28499018

RESUMO

Background: Craniopharyngiomas are frequent hypothalamo-pituitary tumors in children, presenting predominantly as cystic lesions. Morbidity from conventional treatment has focused attention on intracystic drug delivery, hypothesized to cause fewer clinical consequences. However, the efficacy of intracystic therapy remains unclear. We report the retrospective experiences of several global centers using intracystic interferon-alpha. Methods: European Société Internationale d'Oncologie Pédiatrique and International Society for Pediatric Neurosurgery centers were contacted to submit a datasheet capturing pediatric patients with cystic craniopharyngiomas who had received intracystic interferon-alpha. Patient demographics, administration schedules, adverse events, and outcomes were obtained. Progression was clinical or radiological (cyst reaccumulation, novel cysts, or solid growth). Results: Fifty-six children (median age, 6.3 y) from 21 international centers were identified. Median follow-up from diagnosis was 5.1 years (0.3-17.7 y). Lesions were cystic (n = 22; 39%) or cystic/solid (n = 34; 61%). Previous progression was treated in 43 (77%) patients before interferon use. In such cases, further progression was delayed by intracystic interferon compared with the preceding therapy for cystic lesions (P = 0.0005). Few significant attributable side effects were reported. Progression post interferon occurred in 42 patients (median 14 mo; 0-8 y), while the estimated median time to definitive therapy post interferon was 5.8 (1.8-9.7) years. Conclusions: Intracystic interferon-alpha can delay disease progression and potentially offer a protracted time to definitive surgery or radiotherapy in pediatric cystic craniopharyngioma, yet demonstrates a favorable toxicity profile compared with other therapeutic modalities-important factors for this developing age group. A prospective, randomized international clinical trial assessment is warranted.


Assuntos
Craniofaringioma/radioterapia , Interferon-alfa/metabolismo , Neoplasias Hipofisárias/radioterapia , Adolescente , Criança , Pré-Escolar , Craniofaringioma/metabolismo , Feminino , Humanos , Injeções Intralesionais/métodos , Masculino , Estudos Retrospectivos
11.
Sci Rep ; 6: 34375, 2016 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-27708337

RESUMO

Recent advances in cell sorting aim at the development of novel methods that are sensitive to various mechanical properties of cells. Microfluidic technologies have a great potential for cell sorting; however, the design of many micro-devices is based on theories developed for rigid spherical particles with size as a separation parameter. Clearly, most bioparticles are non-spherical and deformable and therefore exhibit a much more intricate behavior in fluid flow than rigid spheres. Here, we demonstrate the use of cells' mechanical and dynamical properties as biomarkers for separation by employing a combination of mesoscale hydrodynamic simulations and microfluidic experiments. The dynamic behavior of red blood cells (RBCs) within deterministic lateral displacement (DLD) devices is investigated for different device geometries and viscosity contrasts between the intra-cellular fluid and suspending medium. We find that the viscosity contrast and associated cell dynamics clearly determine the RBC trajectory through a DLD device. Simulation results compare well to experiments and provide new insights into the physical mechanisms which govern the sorting of non-spherical and deformable cells in DLD devices. Finally, we discuss the implications of cell dynamics for sorting schemes based on properties other than cell size, such as mechanics and morphology.


Assuntos
Deformação Eritrocítica , Eritrócitos/citologia , Citometria de Fluxo/métodos , Feminino , Citometria de Fluxo/instrumentação , Humanos , Masculino
12.
Cytotherapy ; 18(9): 1178-86, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27421737

RESUMO

BACKGROUND AIMS: Atypical rhabdoid/teratoid tumors (AT/RT) are the most common brain tumors in infants and associated with a dismal prognosis. Although intensification of first-line therapy has resulted in improvement of overall survival, novel treatment strategies are needed. Because immunotherapy has resulted in remarkable results in several adult tumor entities, incorporation of immunotherapy into AT/RT treatment offers a novel alternative. METHODS: We retrospectively analyzed data from 7 AT/RT patients from five countries treated within the HGG-Immuno Consortium. Two patients were ≤1 year and 4 patients were ≤2 years of age at diagnosis. All received immunotherapy with autologous, tumor-lysate-loaded dendritic cells (DCs) on a compassionate use basis using a schedule of three to four weekly DC vaccinations with up to 2 × 10(7) DCs per vaccine, followed by three lysate boosts each 1 month apart. RESULTS: Monocyte collections (median age at apheresis 31.5, range 20-143 months) and vaccinations were uneventful without any severe adverse event related to the vaccine, demonstrating feasibility and safety in this very young age group. Two children received immunotherapy during their primary and the remaining five during second- or third-line therapy. Three of seven patients survived long term with a follow-up of 143, 138 and 46 months, with at least two of them harboring somatic mutations. One long-term survivor was vaccinated during primary treatment and the other two after first or second relapse/progression. Two analyzed patients showed positive CD8(+) T-cell responses after vaccination. DISCUSSION: Our data demonstrate that anti-tumor immunotherapy with autologous DCs is feasible and safe in young children with ATRTs and that this approach warrants further investigation in controlled clinical trials.


Assuntos
Neoplasias Encefálicas/terapia , Vacinas Anticâncer/uso terapêutico , Imunoterapia/métodos , Tumor Rabdoide/terapia , Neoplasias Encefálicas/imunologia , Criança , Pré-Escolar , Ensaios de Uso Compassivo , Células Dendríticas/imunologia , Células Dendríticas/transplante , Feminino , Humanos , Lactente , Masculino , Monitorização Imunológica/métodos , Prognóstico , Estudos Retrospectivos , Tumor Rabdoide/imunologia , Inquéritos e Questionários , Resultado do Tratamento
13.
Cell ; 164(5): 1060-1072, 2016 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-26919435

RESUMO

Primitive neuroectodermal tumors of the central nervous system (CNS-PNETs) are highly aggressive, poorly differentiated embryonal tumors occurring predominantly in young children but also affecting adolescents and adults. Herein, we demonstrate that a significant proportion of institutionally diagnosed CNS-PNETs display molecular profiles indistinguishable from those of various other well-defined CNS tumor entities, facilitating diagnosis and appropriate therapy for patients with these tumors. From the remaining fraction of CNS-PNETs, we identify four new CNS tumor entities, each associated with a recurrent genetic alteration and distinct histopathological and clinical features. These new molecular entities, designated "CNS neuroblastoma with FOXR2 activation (CNS NB-FOXR2)," "CNS Ewing sarcoma family tumor with CIC alteration (CNS EFT-CIC)," "CNS high-grade neuroepithelial tumor with MN1 alteration (CNS HGNET-MN1)," and "CNS high-grade neuroepithelial tumor with BCOR alteration (CNS HGNET-BCOR)," will enable meaningful clinical trials and the development of therapeutic strategies for patients affected by poorly differentiated CNS tumors.


Assuntos
Neoplasias do Sistema Nervoso Central/genética , Neoplasias do Sistema Nervoso Central/patologia , Metilação de DNA , Tumores Neuroectodérmicos/genética , Tumores Neuroectodérmicos/patologia , Sequência de Aminoácidos , Neoplasias do Sistema Nervoso Central/classificação , Neoplasias do Sistema Nervoso Central/diagnóstico , Criança , Fatores de Transcrição Forkhead/genética , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Dados de Sequência Molecular , Tumores Neuroectodérmicos/classificação , Tumores Neuroectodérmicos/diagnóstico , Proteínas Proto-Oncogênicas/química , Proteínas Proto-Oncogênicas/genética , Proteínas Repressoras/química , Proteínas Repressoras/genética , Transdução de Sinais , Proteínas Supressoras de Tumor/genética
15.
Biomed Res Int ; 2015: 862039, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26998479

RESUMO

BACKGROUND: AT/RTs are rare aggressive brain tumours, mainly affecting young children. Most cases present with genetic inactivation of SMARCB1, a core member of the SWI/SNF chromatin-remodeling complex. We have performed whole exome- and mRNA-sequencing on an early onset AT/RT case for detection of genetic events potentially contributing to the disease. RESULTS: A de novo germline variant in SMARCB1, c.601C>T p.Arg201∗, in combination with somatic deletion of the healthy allele is likely the major tumour causing event. Only seven somatic small scale mutations were discovered (hitting SEPT03, H2BFM, ZIC4, HIST2H2AB, ZIK1, KRTAP6-3, and IFNA8). All were found with subclonal allele frequencies (range 5.7-17%) and none were expressed. However, besides SMARCB1, candidate genes affected by predicted damaging germline variants that were expressed were detected (KDM5C, NUMA1, and PCM1). Analysis of differently expressed genes revealed many dysregulated pathways in the tumour, such as cell cycle, CXCR4 pathway, GPCR-signalling, and neuronal system. FGFR1, CXCR4, and MDK were upregulated and may represent possible drug targets. CONCLUSION: The loss of SMARCB1 function leads to AT/RT development and deregulated genes and pathways. Additional predisposing events may however contribute. Studies utilizing NGS technologies in larger cohorts will probably identify recurrent genetic and epigenetic alterations and molecular subgroups with implications for clinical practice and development of targeted therapies.


Assuntos
Proteínas Cromossômicas não Histona/deficiência , Proteínas Cromossômicas não Histona/genética , Proteínas de Ligação a DNA/deficiência , Proteínas de Ligação a DNA/genética , Genoma/genética , RNA Mensageiro/genética , Tumor Rabdoide/genética , Teratoma/genética , Fatores de Transcrição/deficiência , Fatores de Transcrição/genética , Proteínas Cromossômicas não Histona/metabolismo , Proteínas de Ligação a DNA/metabolismo , Humanos , Lactente , Masculino , Acúmulo de Mutações , RNA Mensageiro/análise , RNA Mensageiro/metabolismo , Proteína SMARCB1 , Análise de Sequência de DNA , Transdução de Sinais , Fatores de Transcrição/metabolismo
16.
Pediatr Blood Cancer ; 61(9): 1603-9, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24692119

RESUMO

BACKGROUND: Despite major treatment attempts, the prognosis for pediatric diffuse intrinsic pontine gliomas (DIPGs) remains dismal. Gliomas are highly vascularized tumors, suggesting that the prevention of vessel formation by anti-angiogenic treatment might be effective. PROCEDURE: Forty-one pediatric patients with DIPG were treated according to the Angiocomb protocol, starting with radiotherapy combined with topotecan and followed by anti-angiogenic triple medication consisting of thalidomide, etoposide, and celecoxib. Overall survival, radiological response, quality of life, requirement of corticosteroids, and adverse effects were monitored. Eight patients treated with only radiotherapy were used as controls. RESULTS: For study patients, the 12 and 24 months overall survival was 61% and 17%, respectively. The median overall survival was 12 months (range 4-60 months). Four radiological complete responses were seen, of which two were transient. Radiologically, 56% of the tumors reduced in size and 78% in signal intensity. Study patients were able to visit school or daycare and walk for a significantly longer time compared to controls (Log Rank 0.036 and 0.008, respectively). Adverse effects were generally minor. CONCLUSIONS: The Angiocomb protocol created a noticeable share of long-term survivors and was well tolerated, suggesting that anti-angiogenic therapy for patients with DIPG should be studied more in the future.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Tronco Encefálico/terapia , Quimiorradioterapia , Glioma/terapia , Qualidade de Vida , Adolescente , Neoplasias do Tronco Encefálico/mortalidade , Neoplasias do Tronco Encefálico/patologia , Estudos de Casos e Controles , Celecoxib , Quimioterapia Adjuvante , Criança , Pré-Escolar , Etoposídeo/administração & dosagem , Feminino , Seguimentos , Glioma/mortalidade , Glioma/patologia , Humanos , Lactente , Masculino , Gradação de Tumores , Prognóstico , Pirazóis/administração & dosagem , Indução de Remissão , Sulfonamidas/administração & dosagem , Taxa de Sobrevida , Talidomida/administração & dosagem , Topotecan/administração & dosagem
17.
Acta Ophthalmol ; 92(5): 404-11, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24119165

RESUMO

PURPOSE: The aim is to report the 10-year retrospective experience of systemic chemotherapy for a population-based group of patients with hereditary retinoblastoma at a national referral centre. The outcomes include control rates, treatment side-effects, adjuvant therapy, failure rate, survival, secondary cancers and visual acuity. METHODS: All patients (n = 24, 46 eyes) diagnosed with retinoblastoma and treated with systemic chemotherapy at a national referral centre during 2001-2011 were included. Data were extracted from medical records. RESULTS: The patients were followed for a mean of 60 months (range 13-144). Four-six cycles of VEC was administered to all newly diagnosed group B/C/D/E eyes with bilateral disease and 83% (38 of 46) responded to the treatment. None of the patients discontinued chemotherapy because of adverse reactions. Altogether 26% (12 of 46) of the eyes received second-line therapy (other than thermotherapy, cryotherapy and chemotherapy). The failure rate was 35% (16 of 46) and mortality rate 0%. None of the patients developed CNS manifestations (metastases or trilateral retinoblastoma). One of the patients developed a second primary tumour (osteosarcoma) 4 years following retinoblastoma diagnosis. Altogether 17% (4 of 24) patients received radiation therapy, 28% (13 of 46) of the eyes had to be enucleated, and one patient underwent bilateral enucleation. The age-correlated visual acuity was mean of 73% of expected visual acuity. CONCLUSION: Group A/B retinoblastomas have a distinct chemotherapy response, while group C/D/E tumours do not respond as well. The success rate was 65%; while patients have a good prognosis for life, approximately one-third of all hereditary cases received radiation therapy or underwent enucleation.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Retina/tratamento farmacológico , Retinoblastoma/tratamento farmacológico , Carboplatina/uso terapêutico , Pré-Escolar , Terapia Combinada , Crioterapia , Etoposídeo/uso terapêutico , Feminino , Seguimentos , Humanos , Hipertermia Induzida , Lactente , Recém-Nascido , Masculino , Neoplasias da Retina/genética , Neoplasias da Retina/fisiopatologia , Retinoblastoma/genética , Retinoblastoma/fisiopatologia , Estudos Retrospectivos , Resultado do Tratamento , Vincristina/uso terapêutico , Acuidade Visual
18.
Lab Chip ; 12(6): 1048-51, 2012 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-22327631

RESUMO

While size has been widely used as a parameter in cellular separations, in this communication we show how shape and deformability, a mainly untapped source of specificity in preparative and analytical microfluidic devices can be measured and used to separate cells.


Assuntos
Separação Celular/instrumentação , Eritrócitos/citologia , Técnicas Analíticas Microfluídicas/instrumentação , Separação Celular/métodos , Tamanho Celular , Deformação Eritrocítica , Humanos , Técnicas Analíticas Microfluídicas/métodos
19.
Lab Chip ; 11(7): 1326-32, 2011 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-21331436

RESUMO

We present the use of a simple microfluidic technique to separate living parasites from human blood. Parasitic trypanosomatids cause a range of human and animal diseases. African trypanosomes, responsible for human African trypanosomiasis (sleeping sickness), live free in the blood and other tissue fluids. Diagnosis relies on detection and due to their often low numbers against an overwhelming background of predominantly red blood cells it is crucial to separate the parasites from the blood. By modifying the method of deterministic lateral displacement, confining parasites and red blood cells in channels of optimized depth which accentuates morphological differences, we were able to achieve separation thus offering a potential route to diagnostics.


Assuntos
Eritrócitos/parasitologia , Técnicas Analíticas Microfluídicas/métodos , Parasitos/isolamento & purificação , Animais , Humanos , Trypanosoma/isolamento & purificação
20.
PLoS One ; 4(12): e8239, 2009 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-20011509

RESUMO

BACKGROUND: BK and JC polyomaviruses (BKV and JCV) are potentially oncogenic and have in the past inconclusively been associated with tumours of the central nervous system (CNS), while BKV has been hinted, but not confirmed to be associated with neuroblastomas. Recently three new polyomaviruses (KIPyV, WUPyV and MCPyV) were identified in humans. So far KIPyV and WUPyV have not been associated to human diseases, while MCPyV was discovered in Merkel Cell carcinomas and may have neuroepithelial cell tropism. However, all three viruses can be potentially oncogenic and this compelled us to investigate for their presence in childhood CNS and neuroblastomas. METHODOLOGY: The presence of KI, WU and MCPyV DNA was analysed, by a joint WU and KI specific PCR (covering part of VP1) and by a MCPyV specific regular and real time quantitative PCR (covering part of Large T) in 25 CNS tumour biopsies and 31 neuroblastoma biopsies from the Karolinska University Hospital, Sweden. None of the three new human polyomaviruses were found to be associated with any of the tumours, despite the presence of PCR amplifiable DNA assayed by a S14 housekeeping gene PCR. CONCLUSION: In this pilot study, the presence of MCPyV, KI and WU was not observed in childhood CNS tumours and neuroblastomas. Nonetheless, we suggest that additional data are warranted in tumours of the central and peripheral nervous systems and we do not exclude that other still not yet detected polyomaviruses could be present in these tumours.


Assuntos
Neoplasias do Sistema Nervoso Central/virologia , DNA Viral/análise , Células de Merkel/virologia , Neuroblastoma/virologia , Polyomavirus/genética , Adolescente , Anticorpos Antivirais/imunologia , Biópsia , Neoplasias do Sistema Nervoso Central/sangue , Neoplasias do Sistema Nervoso Central/patologia , Criança , DNA Viral/genética , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Neuroblastoma/patologia , Reação em Cadeia da Polimerase , Polyomavirus/imunologia , Suécia
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